TY - JOUR
T1 - Gene-environment interaction as a predictor of early adjustment in first episode psychosis
AU - Fraguas, David
AU - Díaz-Caneja, Covadonga M.
AU - Corripio, Iluminada
AU - González-Pinto, Ana
AU - Lobo, Antonio
AU - Bioque, Miquel
AU - Cuesta, Manuel J.
AU - Sanjuán, Julio
AU - Rodríguez-Toscano, Elisa
AU - Arias, Bárbara
AU - Sarró, Salvador
AU - Cabrera, Bibiana
AU - Bulbena, Antoni
AU - Vieta, Eduard
AU - Castro-Fornieles, Josefina
AU - Arango, Celso
AU - Bernardo, Miquel
AU - Parellada, Mara
PY - 2017/11/1
Y1 - 2017/11/1
N2 - © 2017 Elsevier B.V. Background This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. Methods We constructed a schematic ‘two-hit’ model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the ‘first hit’ and history of obstetric complications and parental socioeconomic status as 'second hits’. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls. Results The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP individuals and in controls, and remained significant after controlling for age, sex, and diagnosis. Conclusions Individuals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.
AB - © 2017 Elsevier B.V. Background This study aims to explore the gene-environment interaction hypothesis applied to pre-symptomatic neurodevelopmental phenotypes of first episode psychosis (FEP), that is, genetic factors might increase vulnerability to the effects of environmental adverse conditions occurring at later stages of development. Methods We constructed a schematic ‘two-hit’ model, with Val/Val homozygosity for the catechol-O-methyltransferase (COMT) Val158Met polymorphism as the ‘first hit’ and history of obstetric complications and parental socioeconomic status as 'second hits’. Early adjustment, measured using the Premorbid Adjustment Scale, was considered the main outcome. The study population comprised 221 adolescents and adults with FEP and 191 sex- and age-matched controls. Results The interaction between the Val/Val COMT genotype and a positive history of obstetric complications plus low parental socioeconomic status was significantly associated with poorer early adjustment. These results were observed both in FEP individuals and in controls, and remained significant after controlling for age, sex, and diagnosis. Conclusions Individuals carrying Val/Val seem to be more sensitive to the synergistic effect of environmental factors acting early in neurodevelopment, which leads to vulnerability phenotypes such as impaired early adjustment.
KW - COMT
KW - Obstetric complications
KW - Parental socioeconomic status
KW - Premorbid adjustment
KW - Schizophrenia
U2 - 10.1016/j.schres.2017.02.021
DO - 10.1016/j.schres.2017.02.021
M3 - Article
SN - 0920-9964
VL - 189
SP - 196
EP - 203
JO - Schizophrenia Research
JF - Schizophrenia Research
ER -